Background: Approximately 9.8 million cancer survivors are alive in the United States today. Enthusiasm for prescribing physical activity for cancer survivors depends on evidence regarding whether physical activity during or after completion of treatment results in improved outcomes such as cardiorespiratory fitness, fatigue, symptoms, quality of life, mental health, or change in body size. Methods: A systematic qualitative and quantitative review of the English language scientific literature identified controlled trials of physical activity interventions in cancer survivors during and after treatment. Data from 32 studies were abstracted, weighted mean effect sizes (WMES) were calculated from the 22 high-quality studies, and a systematic level of evidence criteria was applied to evaluate 25 outcomes. Results: There was qualitative and quantitative evidence of a small to moderate effect of physical activity interventions on cardiorespiratory fitness (WMES = 0.51 and 0.65 during and after treatment respectively, P < 0.01), physiologic outcomes and symptoms during treatment (WMES = 0.28, P < 0.01 and 0.39, P < 0.01, respectively), and vigor posttreatment (WMES = 0.83, P = 0.04). Physical activity was well tolerated in cancer survivors during and after treatment, but the available literature does not allow conclusions to be drawn regarding adverse events from participation. Conclusions: Physical activity improves cardiorespiratory fitness during and after cancer treatment, symptoms and physiologic effects during treatment, and vigor posttreatment. Additional physical activity intervention studies are needed to more firmly establish the range and magnitude of positive effects of physical activity among cancer survivors.